Differential regulation of primary and memory CD8 T cell immune responses by diacylglycerol kinases.
The manipulation of signals downstream of the TCR can have profound consequences for T cell development, function, and homeostasis. Diacylglycerol (DAG) produced after TCR stimulation functions as a secondary messenger and mediates the signaling to Ras-MEK-Erk and NF-κB pathways in T cells. DAG kinases (DGKs) convert DAG into phosphatidic acid, resulting in termination of DAG signaling. In this study, we demonstrate that DAG metabolism by DGKs can serve a crucial function in viral clearance upon lymphocytic choriomeningitis virus infection. Ag-specific CD8(+) T cells from DGKα(-/-) and DGKζ(-/-) mice show enhanced expansion and increased cytokine production after lymphocytic choriomeningitis virus infection, yet DGK-deficient memory CD8(+) T cells exhibit impaired expansion after rechallenge. Thus, DGK activity plays opposing roles in the expansion of CD8(+) T cells during the primary and memory phases of the immune response, whereas consistently inhibiting antiviral cytokine production.
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- Mice, Transgenic
- Mice, Knockout
- Mice
- Lymphocytic choriomeningitis virus
- Lymphocytic Choriomeningitis
- Immunology
- Immunologic Memory
- Epitopes, T-Lymphocyte
- Down-Regulation
- Disease Models, Animal
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Mice, Transgenic
- Mice, Knockout
- Mice
- Lymphocytic choriomeningitis virus
- Lymphocytic Choriomeningitis
- Immunology
- Immunologic Memory
- Epitopes, T-Lymphocyte
- Down-Regulation
- Disease Models, Animal